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Fertility preservation in the cancer setting, known as oncofertility, is a field that requires cross-disciplinary interaction between physicians, basic scientists, clinical researchers, ethicists, lawyers, educators, and religious leaders. Funded by the National Institutes of Health, the Oncofertility Consortium (OC) was formed to be a scientifically grounded, transparent, and altruistic resource, both intellectual and monetary, for building this new field of practice capable of addressing the unique needs of young patients with cancer. The OC has expanded its attention to include other nonmalignant conditions that can threaten fertility, and the work of the OC now extends around the globe, involving partners who together have created a community of shared effort, resources, and practices. The OC creates materials that are translated, disseminated, and amended by all participants in the field, and local programs of excellence have developed worldwide to accelerate the pace and improve the quality of oncofertility research and practice. Here we review the global oncofertility programs and the capacity building activities that strengthen these research and clinical programs, ultimately improving patient care.

Introduction Autosomal dominant polycystic kidney disease (ADPKD) causes kidney failure typically in adulthood, but the disease starts in utero. Copeptin, epidermal growth factor (EGF), and monocyte chemoattractant protein-1 (MCP-1) are associated with severity and hold prognostic value in adults but remain unstudied in the early disease stage. Kidneys from adults with ADPKD exhibit macrophage infiltration, and a prominent role of MCP-1 secretion by tubular epithelial cells is suggested from rodent models. Methods In a cross-sectional study, plasma copeptin, urinary EGF, and urinary MCP-1 were evaluated in a pediatric ADPKD cohort and compared with age-, sex-, and body mass index (BMI)-matched healthy controls. MCP-1 was studied in mouse collecting duct cells, human proximal tubular cells, and fetal kidney tissue. Results Fifty-three genotyped ADPKD patients and 53 controls were included. The mean (SD) age was 10.4 (5.9) versus 10.5 (6.1) years (P = 0.543), and the estimated glomerular filtration rate (eGFR) was 122.7 (39.8) versus 114.5 (23.1) ml/min per 1.73 m2 (P = 0.177) in patients versus controls, respectively. Plasma copeptin and EGF secretion were comparable between groups. The median (interquartile range) urinary MCP-1 (pg/mg creatinine) was significantly higher in ADPKD patients (185.4 [213.8]) compared with controls (154.7 [98.0], P = 0.010). Human proximal tubular cells with a heterozygous PKD1 mutation and mouse collecting duct cells with a PKD1 knockout exhibited increased MCP-1 secretion. Human fetal ADPKD kidneys displayed prominent MCP-1 immunoreactivity and M2 macrophage infiltration. Conclusion An increase in tubular MCP-1 secretion is an early event in ADPKD. MCP-1 is an early disease severity marker and a potential treatment target., Graphical abstract

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The application of next-generation sequencing to fetal pathology has proved to increase the diagnostic yield in fetuses with abnormal ultrasounds. We retrospectively reviewed genetic data of 30 selected cases studied through targeted resequencing of OMIM genes. In our experience, clinical data proved to be essential to support diagnostic reasoning and enhance variants’ assessment. The molecular diagnosis was reached in 19/30 (63%) cases. Only in 7/19 cases the molecular diagnosis confirmed the initial diagnostic hypothesis, showing the relevance of the genotype-first approach. According to the genotype-phenotype correlation, we were able to divide the solved cases into three groups: i) the correlation is well established but it was missed due to lack of specificity, unusual presentation or recent description; ii) the clinical presentation is much more severe than currently known for the underlying condition; iii) the correlation does not recapitulate the entire phenotype, possibly due to the fetal presentation or multiple coexisting conditions. Moreover, we found a higher proportion of recessive diagnosis in abnormal fetuses compared to cohorts of individuals with developmental delay. Our findings suggest that fetal pathology may be enriched in rare alleles and/or in unusual combinations, counter-selected in postnatal genomes and thus contributing to both phenotypic extremeness and atypical presentation.

Study question Does extended culture to the blastocyst stage affect singleton birthweight after either fresh or vitrified-warmed embryo transfer? Summary answer Singleton birthweight z-scores did not vary significantly after a fresh blastocyst transfer, whereas the additional effect of vitrification remains inconclusive. What is known already Observational studies have associated extended culture with an increased risk of preterm birth and low birthweight. On the contrary, in terms of birthweight and gestational age, singletons born after vitrification have been associated with a better perinatal outcome when compared to those born following a fresh transfer. Study design, size, duration Our post-hoc cohort analysis on neonatal outcomes included 447 liveborn singletons was derived from a recent retrospective analysis on cumulative live birth rates after cleavage-stage and blastocyst transfers. These babies were born following a fresh single cleavage-stage transfer (FCT Day 3, n = 113), fresh single blastocyst transfer (FBT Day 5, n = 218), vitrified-warmed cleavage-stage transfer (VCT Day 3, n = 58) or vitrified-warmed blastocyst transfer (VBT Day 5, n = 58). Participants/materials, setting, methods Singleton birthweight was the primary outcome measure. Gestational age and gender of the newborn were accounted for by using birthweight z-scores in a multivariable linear regression analysis, adjusting for other confounders (maternal age, BMI, parity and smoking behaviour). Vanishing twins were excluded from the analysis. Main results and the role of chance A significantly lower z-score was observed after blastocyst transfer compared to cleavage-stage transfer in the vitrified-warmed Day 5 group (P = 0.013), a difference not observed in the fresh transfer groups (P = 0.32). Following multivariable regression analysis [adjusted regression coefficient (95% confidence interval)], the FCT and FBT groups showed no significant influence on the birthweight z-scores after fresh transfer [-0.19 (-0.44; 0.05)], but the transfer of vitrified blastocysts (VBT) was associated with a lower birthweight [-0.52 (-0.90; -0.15)] compared with the transfer of vitrified cleavage-stage embryos (VCT). Limitations, reasons for caution The present cohort was relatively small, especially in the vitrified-warmed subgroups. Pregnancy-associated factors possibly influencing birthweight (such as diabetes, hypertension, pre-eclampsia) were also not accounted for in the analysis. Wider implications of the findings Different ART procedures, including extended culture and vitrification, may hold potential safety issues. These results require further confirmation in future larger studies. Study funding/competing interest(s) None. Trial registration number N/A.

Study question Are meiotic and developmental competence of human oocytes from small (2-8 mm) antral follicles improved by applying an optimized IVM method involving a prematuration step in presence of C-Type Natriuretic Peptide (CNP) followed by a maturation step in presence of FSH and Amphiregulin (AREG)? Summary answer A strategy involving prematuration culture (PMC) in the presence of CNP followed by IVM using FSH + AREG increases oocyte maturation potential leading to a higher availability of Day 3 embryos and good-quality blastocysts for single embryo transfer. What is known already IVM is a minimal-stimulation ART with reduced hormone-related side effects and risks for the patients, but the approach is not widely used because of an efficiency gap compared to conventional ART. In vitro systems that enhance synchronization of nuclear and cytoplasmic maturation before the meiotic trigger are crucial to optimize human IVM systems. However, previous PMC attempts have failed in sustaining cumulus-oocyte connections throughout the culture period, which prohibited a normal cumulus-oocyte communication and precluded an adequate response by the cumulus-oocyte complex (COC) to the meiotic trigger. Study design, size, duration A first prospective study involved sibling oocytes from a group of 15 patients with polycystic ovary syndrome (PCOS) to evaluate effects of a new IVM culture method on oocyte nuclear maturation and their downstream developmental competence. A second prospective study in an additional series of 15 women with polycystic ovaries characterized and fine-tuned the culture conditions. Participants/materials, setting, methods Fifteen women with PCOS (according to Rotterdam criteria) underwent IVM treatment after 3-5 days of highly purified human menopausal gonadotropin (HP-hMG) stimulation and no human chorionic gonadotropin (hCG) trigger before oocyte retrieval. A first study was designed with sibling oocytes to prospectively evaluate the impact of an IVM culture method: 24 h PMC with CNP + 30 h IVM with FSH and AREG, on embryo yield, in comparison to the standard (30 h) IVM clinical protocol (Group I, n = 15). A second prospective study was performed in 15 women with polycystic ovaries, to characterize and optimize the PMC conditions (Group II, n = 15). The latter study involved the evaluation of oocyte meiotic arrest, the preservation of cumulus-oocyte transzonal projections (TZPs), the patterns of oocyte chromatin configuration and cumulus cells apoptosis following the 24 and 46 h PMC. Furthermore, oocyte developmental potential following PMC (24 and 46 h) + IVM was also evaluated. The first 20 good-quality blastocysts from PMC followed by IVM were analysed by next generation sequencing to evaluate their aneuploidy rate. Main results and the role of chance PMC in presence of CNP followed by IVM using FSH and AREG increased the meiotic maturation rate per COC to 70%, which is significantly higher than routine standard IVM (49%; P ≤ 0.001). Hence, with the new system the proportion of COCs yielding transferable Day 3 embryos and good-quality blastocysts increased compared to routine standard IVM (from 23 to 43%; P ≤ 0.001 and from 8 to 18%; P ≤ 0.01, respectively). CNP was able to prevent meiosis resumption for up to 46 h. After PMC, COCs had preserved cumulus-oocyte TZPs. The blastocysts obtained after PMC + IVM did not show increased aneuploidy rates as compared to blastocysts from conventional ART. Limitations reasons for caution The novel IVM approach in PCOS patients was tested in oocytes derived from small antral follicles which have an intrinsically low developmental potential. Validation of the system would be required for COCs from different (larger) follicular sizes, which may involve further adjustment of PMC conditions. Furthermore, considering that this is a novel strategy in human IVM treatment, its global efficiency needs to be confirmed in large prospective randomized controlled trials. The further application in infertile patients without PCOS, e.g. cancer patients, remains to be evaluated. Wider implications of the findings The findings of this pilot study suggest that the efficiency gap between IVM and conventional IVF can be reduced by fine-tuning of the culture methods. This novel strategy opens new perspectives for safe and patient-friendly ART in patients with PCOS. Study funding/competing interest(s) IVM research at the Vrije Universiteit Brussel has been supported by grants from: the Institute for the Promotion of Innovation by Science and Technology in Flanders (Agentschap voor Innovatie door Wetenschap en Technologie-IWT, project 110680); the Fund for Research Flanders (Fonds Wetenschappelijk Onderzoek-Vlaanderen-FWO, project G.0343.13), the Belgian Foundation Against Cancer (HOPE project, Dossier C69). The authors have no conflicts of interest.

Prospective studies comparing different durations of progesterone supplementation before transfer of vitrified-warmed blastocysts in an artificial cycle are lacking. However, in oocyte donation programmes, the sporadic available evidence demonstrates considerable differences in clinical pregnancy rates according to the duration of progesterone administration. This randomised controlled trial (RCT), included 303 patients undergoing a frozen-thawed embryo transfer (FET) of one or two vitrified-warmed blastocyst(s) in an artificial cycle. Randomisation was performed when the endometrial thickness reached ≥7 mm after oestrogen supplementation. One hundred and fifty two patients in group A received 7 d of vaginal micronised progesterone tablets and 151 patients in group B received 5 d of micronised vaginal progesterone before FET. No differences were seen in clinical pregnancy rate between both groups: 42/152 (27.6%) in group A versus 49/151 (32.5%) in group B. Although no statistically significant difference was observed in clinical pregnancy rates, our study was powered to detect an absolute difference of 16%. In this regard, we cannot exclude that smaller, clinically relevant differences might exist and our study did not have the power to detect this. Patients were also not blinded for the intervention, causing a potential bias.

Deletions on the long arm of the Y chromosome are a well-known cause of male infertility and it is generally accepted that deletions involving the AZFb region are not compatible with sperm production. Here, we report on two patients for whom basic diagnostic tests showed a deletion of the AZFb region. Unexpectedly, both patients had some residual sperm production. Subsequently, extension and additional analyses of the AZFb region disclosed an aberrant deletion pattern. Therefore, these results emphasize the need for a detailed and powerful analysis of cases where first-line Yq deletion tests reveal an AZFb deletion. Moreover, our study clearly demonstrated that only a very careful selection of test markers will avoid the pitfall of a 'no further treatment possible' wrongful conclusion.

Study question What is the semen quality of young adult men who were conceived 18-22 years ago by ICSI for male infertility? Summary answer In this cohort of 54 young adult ICSI men, median sperm concentration, total sperm count and total motile sperm count were significantly lower than in spontaneously conceived peers. What is known already The oldest ICSI offspring cohort worldwide has recently reached adulthood. Hence, their reproductive health can now be investigated. Since these children were conceived by ICSI because of severe male-factor infertility, there is reasonable concern that male offspring have inherited the deficient spermatogenesis from their fathers. Previously normal pubertal development and adequate Sertoli and Leydig cell function have been described in pubertal ICSI boys; however, no information on their sperm quality is currently available. Study design, size, duration This study was conducted at UZ Brussel between March 2013 and April 2016 and is part of a large follow-up project focussing on reproductive and metabolic health of young adults, between 18 and 22 years and conceived after ICSI with ejaculated sperm. Results of both a physical examination and semen analysis were compared between young ICSI men being part of a longitudinally followed cohort and spontaneously conceived controls who were recruited cross-sectionally. Participants/materials, setting, method Results of a single semen sample in 54 young adult ICSI men and 57 spontaneously conceived men are reported. All young adults were individually assessed, and the results of their physical examination were completed by questionnaires. Data were analysed by multiple linear and logistic regression, adjusted for covariates. In addition, semen parameters of the ICSI fathers dating back from their ICSI treatment application were analysed for correlations. Main results and the role of chance Young ICSI adults had a lower median sperm concentration (17.7 million/ml), lower median total sperm count (31.9 million) and lower median total motile sperm count (12.7 million) in comparison to spontaneously conceived peers (37.0 million/ml; 86.8 million; 38.6 million, respectively). The median percentage progressive and total motility, median percentage normal morphology and median semen volume were not significantly different between these groups. After adjustment for confounders (age, BMI, genital malformations, time from ejaculation to analysis, abstinence period), the statistically significant differences between ICSI men and spontaneously conceived peers remained: an almost doubled sperm concentration in spontaneously conceived peers in comparison to ICSI men (ratio 1.9, 95% CI 1.1-3.2) and a two-fold lower total sperm count (ratio 2.3, 95% CI 1.3-4.1) and total motile count (ratio 2.1, 95% CI 1.2-3.6) in ICSI men compared to controls were found. Furthermore, compared to men born after spontaneous conception, ICSI men were nearly three times more likely to have sperm concentrations below the WHO reference value of 15 million/ml (adjusted odds ratio (AOR) 2.7; 95% CI 1.1-6.7) and four times more likely to have total sperm counts below 39 million (AOR 4.3; 95% CI 1.7-11.3). In this small group of 54 father-son pairs, a weak negative correlation between total sperm count in fathers and their sons was found. Limitations, reasons for caution The main limitation is the small study population. Also, the results of this study where ICSI was performed with ejaculated sperm and for male-factor infertility cannot be generalized to all ICSI offspring because the indications for ICSI have nowadays been extended and ICSI is also being performed with non-ejaculated sperm and reported differences may thus either decrease or increase. Wider implications of the findings These first results in a small group of ICSI men indicate a lower semen quantity and quality in young adults born after ICSI for male infertility in their fathers. Study funding/competing interests This study was supported by Methusalem grants and by grants from Wetenschappelijk Fonds Willy Gepts, all issued by the Vrije Universiteit Brussel (VUB). All co-authors except M.B. and H.T. declared no conflict of interest. M.B. has received consultancy fees from MSD, Serono Symposia and Merck. The Universitair Ziekenhuis Brussel (UZ Brussel) and the Centre for Medical Genetics have received several educational grants from IBSA, Ferring, Organon, Shering-Plough and Merck for establishing the database for follow-up research and organizing the data collection. The institution of H.T. has received research grants from the Research Fund of Flanders (FWO), an unconditional grant from Ferring for research on testicular stem cells and research grants from Ferring, Merck, MSD, Roche, Besins, Goodlife and Cook for several research projects in female infertility. H.T. has received consultancy fees from Finox, Abbott and ObsEva for research projects in female infertility.

OBJECTIVE: The benefit of performing an appendectomy during the surgical treatment of a mucinous borderline ovarian tumor (mBOT) is still controversial, even though clinical guidelines recommend this procedure. PURPOSE: Our aim was to systematically assess the available evidence on appendectomy in the case of diagnosis of mBOT. METHODS: A comprehensive search of the literature was conducted using electronic databases using the search terms: (borderline OR low malignant potential) AND (appendectomy OR appendix). RESULTS: A total of 12 articles were retained after systematic review, including a total of 667 patients with borderline ovarian tumor. Appendectomy was performed in 232 of the patients presenting with a mBOT. Two (0.86 %) appendiceal carcinomas were confirmed on pathological examination. Both appendices were grossly abnormal at the time of surgery. CONCLUSION: Our systematic review demonstrates that available evidence regarding the role of appendectomy in mBOT is fragmented and weak. Nevertheless,this review provides adequate evidence to highlight that appendiceal involvement in mBOTs appears to be extremely rare and microscopic appendiceal involvement is highly unlikely in apparently normal appendices. In spite of the diversity of the included studies, the lack of appendiceal involvement in all cases with apparently normal appendix is strikingly common. We can conclude that in the case of normal appearance of the appendix at the time of primary surgery, appendectomy is not mandatory. Furthermore, a patient with a normal appendiceal appearance during primary surgery with post-operative diagnosis of mBOT addition of a second look intervention seems unnecessary and even hazardous.

OBJECTIVE: To predict sensorineural hearing loss (SNHL) and neurological impairment in congenital cytomegalovirus (cCMV) infection using MR imaging and define the best timing in pregnancy for prenatal assessment. METHODS: In 121 patients with confirmed cCMV infection, brain features at MR imaging were respectively graded from 1 to 5: normal; isolated frontal/parieto-occipital hyperintensity; temporal periventricular hyperintensity; temporal/occipital cysts and/or intraventricular septa; migration disorders. Grading was correlated with postnatal SNHL and neurological impairment using regression analysis. In 51 fetuses with MR examinations at 26.9 and 33.0 weeks, the predictive value of SNHL and neurological impairment was compared using ROC curves. RESULTS: Postnatal follow-up showed SNHL in 18 infants and neurological impairment in 10. MR grading was predictive of SNHL and of neurological impairment (P

Study question When does germ cell loss and fibrosis occur in patients with Klinefelter syndrome (KS)? Summary answer In KS, germ cell loss is not observed in testicular tissue from fetuses in the second semester of pregnancy but present at a prepubertal age when the testicular architecture is still normal, while fibrosis is highly present at an adolescent age. What is known already Most KS patients are azoospermic at adult age because of a massive germ cell loss. However, the timing when this germ cell loss starts is not known. It is assumed that germ cell loss increases at puberty. Therefore, testicular sperm extraction (TESE) at an adolescent age has been suggested to increase the chances of sperm retrieval at onset of spermatogenesis. However, recent data indicate that testicular biopsies from peripubertal KS patients contain only a few germ cells. Study design, size, duration In this study, we give an update on fertility preservation in adolescent KS patients and evaluate whether fertility preservation would be beneficial at prepubertal age. The possibility of retrieving testicular spermatozoa by TESE was evaluated in adolescent and adult KS men. The presence of spermatogonia and the degree of fibrosis were also analysed in testicular biopsies from KS patients at different ages. The patients were divided into four age groups: foetal (n = 5), prepubertal (aged 4-7 years; n = 4), peripubertal (aged 12-16 years; n = 20) and adult (aged 18-41 years; n = 27) KS patients. Participants/materials, setting, methods In peripubertal and adult KS patients, retrieval of spermatozoa was attempted by semen analysis after masturbation, vibrostimulation, electroejaculation or by TESE. MAGE-A4 immunohistochemistry was performed to evaluate the presence of germ cells in testicular biopsies from foetal, prepubertal, peripubertal and adult KS patients. Tissue morphology was evaluated by haematoxylin-periodic acid Schiff (H/PAS) staining. Main results and the role of chance Testicular spermatozoa were collected by TESE in 48.1% of the adult KS patients, while spermatozoa were recovered after TESE in only one peripubertal patient (5.0%). Germ cells were detectable in testicular biopsies from 21% of adult men for whom no spermatozoa could be retrieved by TESE and in 31.5% of peripubertal KS boys. Very small numbers of spermatogonia (0.03-0.06 spermatogonia/tubule) were detected in three out of four (75%) prepubertal patients. At a foetal age, the number of germ cells was similar for KS and control samples. Increased signs of fibrosis were not present at foetal and prepubertal ages, but peripubertal and adult KS patients showed high levels of fibrosis. Large scale data N/A. Limitations, reasons for caution Only four prepubertal biopsies were included in this study, but they all showed a very low germ cell number. A high variability in the number of spermatogonia per mm2 was observed in the limited (n = 5) number of foetal biopsies. However, testicular biopsies from prepubertal and foetal Klinefelter patients are difficult to obtain. Wider implications of the findings Testicular tissue banking at a prepubertal age has been suggested as a potential method for fertility preservation in early diagnosed KS boys. However, our results show that a reduction in germ cell number has already taken place in childhood. Therefore, offering testicular tissue banking in young KS boys to prevent subsequent sterility might be a questionable strategy. However, this should be confirmed in a larger study population. Study funding/competing interest(s) This project was funded by the scientific Fund Willy Gepts from the UZ Brussel (D.V.S., J.D.S.), grants from the Vrije Universiteit Brussel (E.G.) and a Methusalem grant (K.S.). D.V.S is a post-doctoral fellow of the Fonds Wetenschappelijk Onderzoek (FWO; 12M2815N). No conflict of interest is declared.

BACKGROUND: The death of a child before or shortly after birth is frequently preceded by an end-of-life decision (ELD). Population-based studies of incidence and characteristics of ELDs in neonates and infants are rare, and those in the foetal-infantile period (> 22 weeks of gestation - 1 year) including both neonates and stillborns, are non-existent. However, important information is missed when decisions made before birth are overlooked. Our study protocol addresses this knowledge gap. METHODS: First, a new and encompassing framework was constructed to conceptualise ELDs in the foetal-infantile period. Next, a population mortality follow-back survey in Flanders (Belgium) was set up with physicians who certified all death certificates of stillbirths from 22 weeks of gestation onwards, and infants under the age of a year. Two largely similar questionnaires (stillbirths and neonates) were developed, pilot tested and validated, both including questions on ELDs and their preceding decision-making processes. Each death requires a postal questionnaire to be sent to the certifying physician. Anonymity of the child, parents and physician is ensured by a rigorous mailing procedure involving a lawyer as intermediary between death certificate authorities, physicians and researchers. Approval by medical societies, ethics and privacy commissions has been obtained. DISCUSSION: This research protocol is the first to study ELDs over the entire foetal-infantile period on a population level. Based on representative samples of deaths and stillbirths and applying a trustworthy anonymity procedure, the research protocol can be used in other countries, irrespective of legal frameworks around perinatal end-of-life decision-making. ispartof: BMC PEDIATRICS vol:18 issue:1 ispartof: location:England status: published

STUDY QUESTION: What is the effect of artificial shrinkage by laser-induced collapse before vitrification on the implantation potential after transfer of vitrified-warmed blastocysts? SUMMARY ANSWER: The artificial shrinkage by laser-induced collapse did not significantly increase the implantation rate per transferred collapsed blastocyst (37.6%) compared with non-collapsed blastocysts (28.9%) [odds ratio (OR): 1.48, 95% confidence interval (CI): 0.78-2.83]. WHAT IS KNOWN ALREADY: Retrospective studies have demonstrated that artificial shrinkage of the blastocyst prior to vitrification can have a positive effect on blastocyst survival after warming. A recent study found a similar survival rate but higher implantation rate for collapsed blastocysts. So far, no randomized controlled trial has been conducted to investigate the implantation potential of collapsed blastocysts. STUDY DESIGN, SIZE, DURATION: Prospective randomized trial. Patients were recruited from December 2011 until April 2014 and warming cycles were included until July 2014. Patients were randomized in the fresh cycle if blastocysts were available for vitrification and were allocated to the study or control arm according to a computer-generated list. In the study group, blastocysts underwent laser-induced collapse before vitrification. In the control group, blastocysts were vitrified without collapsing. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 443 patients signed informed consent and 270 patients had blastocysts vitrified. One-hundred and thirty-five patients were allocated to the study group and 135 to the control group. Sixty-nine patients from the study group and 69 from the control group returned for at least one warming cycle in which 85 and 93 blastocysts were warmed in the first cycle, respectively. Primary outcome was implantation rate per embryo transferred in the first warming cycle. Secondary outcomes were survival and transfer rates, blastocyst quality after warming, clinical pregnancy rate and implantation rate per warmedblastocyst. Blastocysts were vitrified-warmed one by one using closed vitrification and one or two blastocysts were transferred per warming cycle. MAIN RESULTS AND THE ROLE OF CHANCE: We calculated that the group sample sizes of 80 embryos in the collapse group and 80 embryos in the control group were needed to achieve 80% power to detect a difference between the group proportions of +20% with P < 0.05. In the study group, 69 first warming cycles resulted in 69 transfers with 1.2 blastocysts (n = 85) transferred. In the control group, an average of 1.3 blastocysts (n = 83) were transferred in 67 out of 69 warming cycles. Implantation rates per embryo transferred in the first warming cycle were not different between both groups (38 versus 29%, OR: 1.48; 95% CI: 0.78-2.83), neither was the implantation rate per warmed embryo (38 versus 26%, OR: 1.74; 95% CI: 0.92-3.29). When all warming cycles were considered (n = 135 in each group), survival rate after collapse was significantly higher compared with the control group (98.0 versus 92.0%, OR: 4.25; 95% CI: 1.19-15.21). Furthermore, a higher percentage of high-quality blastocysts (36.3 versus 23.5%, OR: 1.86; 95% CI: 1.12-3.08) and hatching blastocysts (19.2 versus 5.4%, OR: 4.18; 95% CI: 1.84-9.52) were found compared with the control group. LIMITATIONS, REASONS FOR CAUTION: The study lasted more than 2.5 years since fewer patients than expected returned for a warming cycle because of the high ongoing pregnancy rates in the fresh IVF/ICSI cycle. WIDER IMPLICATIONS OF THE FINDINGS: Although no significant higher implantation rate was found after collapse, the better survival and post-warm embryo quality convinced us to recognize a clinical benefit of artificial shrinkage and to implement it in routine vitrification practice. TRIAL REGISTRATION NUMBER: NCT01980225, www.clinicaltrials.gov. The first patient was included November 2011 and the study was registered October 2013.

Background: The use of GnRH analogue medication is essential in reproductive medicine to avoid premature ovulation by pituitary suppression for the duration of ovarian stimulation by gonadotrophins. The type of pituitary suppression by either GnRH agonist analogues versus GnRH antagonist analogues may result in different embryological hence clinical results. Preimplantation genetic diagnosis is a subtype of IVF in which embryos are created for genetic diagnosis of hereditary disorders in order to avoid genetically affected children. Embryological quality hence ovarian stimulation in preimplantation genetic diagnosis is crucial as genetic selection will reduce the number of available embryos to a fraction of the total. Objective: The aim of this study was to assess the efficiency of GnRH antagonist versus GnRH agonist treatment for pituitary suppression in ovarian stimulation for PGD, by proxy of number and quality of embryos at cleavage stage available for biopsy. Method: We conducted a prospective randomisedcontrolled trial comparing pituitary suppression by GnRH antagonist versus GnRH agonist in ovarian stimulation for PGD. The primary outcome measure was the number of embryos of sufficient quality for biopsy at cleavage stage. Secondary outcome parameters were the number of blastocysts available of top quality, and clinical pregnancy rate. Results: There was no difference in number of oocytes retrieved, embryos at cleavage stage available for biopsy or embryo quality. The clinical pregnancy rate was higher in the GnRH agonist group; however the sample size was insufficient to allow conclusions. Conclusion: The use of GnRH agonist versus antagonist treatment does not result in differences in a number of oocytes, embryos or embryo quality in ovarian stimulation for preimplantation genetic diagnosis.

Background The role of elevated baseline progesterone (P) levels in outcomes of frozen embryo transfers (FET) performed in an artificial cycle has not been investigated yet. Objective To evaluate the role of elevated P in artificial FET. Method Case series study of 12 patients with high P levels undergoing artificial FET recruited during a 6-month period in a tertiary referral center. Results The clinical pregnancy rate per transfer was 4/12 (33.3%). The biochemical pregnancy rate was 6/12 (50.0%). Conclusion Elevated levels of P do not seem to have a negative impact on reproductive outcome, and may even be associated with high clinical and biochemical pregnancy rates. Further prospective or large retrospective studies are required to examine the clinical importance of our findings in a larger population.

STUDY QUESTION: What is the prevalence of chromosomal abnormalities in azoospermic men and what are the clinical consequences in terms of increased risk for absent spermatogenesis, miscarriages and offspring with congenital malformations?SUMMARY ANSWER: The prevalence of chromosomal abnormalities in azoospermia was 14.4%, and the number of azoospermic men needed to be screened (NNS) to identify one man with a chromosomal abnormality with increased risk for absence of spermatogenesis was 72, to prevent one miscarriage 370-739 and to prevent one child with congenital malformations 4751-23 757.WHAT IS KNOWN ALREADY: Infertility guidelines worldwide advise screening of non-iatrogenic azoospermic men for chromosomal abnormalities, but only few data are available on the clinical consequences of this screening strategy.STUDY DESIGN, SIZE, DURATION: This retrospective multicentre cross-sectional study of non-iatrogenic azoospermic men was performed at the University Hospital Brussels, Belgium, and the University Medical Centre Groningen, The Netherlands, between January 2000 and July 2016.PARTICIPANTS/MATERIALS, SETTING, METHODS: Analysis of clinical registries retrospectively identified 1663 non-iatrogenic azoospermic men with available results of karyotyping and FSH serum levels. Iatrogenic azoospermia was an exclusion criterion, defined as azoospermia after spermatotoxic medical treatment, exogenous androgen suppletion or vasectomy and/or vasovasostomy. Also, men with a clinical diagnosis of anejaculation or hypogonadotropic hypo-androgenism and/or FSH values = 10 U/l) azoospermia. We estimated the NNS for chromosomal abnormalities to identify one man with absence of spermatogenesis and to prevent one miscarriage or one child with congenital malformations, and calculated the surgical sperm retrieval rates per chromosomal abnormality.MAIN RESULTS AND THE ROLE OF CHANCE: The overall prevalence of chromosomal abnormalities in azoospermia was 14.4% (95% CI 12.7-16.1%), its prevalence being higher in hypergonadotropic azoospermia (20.2%, 95% CI 17.8-22.7%) compared to normogonadotropic azoospermia (4.9%, 95% CI 3.2-6.6%, P LIMITATIONS, REASONS FOR CAUTION: The absolute number of chromosomal abnormalities associated with clinical consequences and adverse pregnancy outcomes in our study was limited, thereby increasing the role of chance. Further, as there are currently no large series on outcomes of pregnancies in men with chromosomal abnormalities, our conclusions are partly based on assumptions derived from the literature.WIDER IMPLICATIONS OF THE FINDINGS: The NNS found can be used in future cost-effectiveness studies and the evaluation of current guidelines on karyotyping in non-iatrogenic azoospermia.

Although the technique of intracytoplasmic sperm injection (ICSI) has been a revolution in the alleviation of male infertility, the use of testicular sperm for ICSI was a formerly unseen breakthrough in the treatment of the azoospermic man with primary testicular failure. At the clinical level, different procedures of testicular sperm retrieval (conventional TESE, micro-TESE, FNA/TESA, MESA, PESA) are being performed, the choice is mainly based on the cause of azoospermia (obstructive versus non-obstructive) and the surgeon's skills. At the level of the IVF laboratory, mechanical procedures to harvest the sperm from the tissue may be combined with enzymatic treatment in order to increase the sperm recovery rates. A number of techniques have been developed for viable sperm selection in males with only immotile testicular sperm available. However, large, well-designed studies on the benefit and safety of one over the other technique are lacking. Despite all the available methods and combinations of laboratory procedures which have a common goal to maximize sperm recovery from testicular samples, a large proportion of NOA patients fail to father a genetically own child. Advanced technology application may improve recovery rates by detection of the testicular foci with active spermatogenesis and/or identification of the rare individual sperm in the testicular suspensions. On the other hand, in vitro spermatogenesis or sperm production from embryonic stem cells or induced pluripotent stem cells might be future options. The present review summarizes the available strategies which aim to maximize sperm recovery from surgically retrieved samples.Bien que la technique d’injection intra cytoplasmique d’un spermatozoïde (ICSI) ait constitué une révolution dans le soulagement de l’infertilité masculine, l’utilisation de spermatozoïdes testiculaires lors de l’ICSI fut une découverte capitale auparavant inaperçue du traitement de l’homme azoospermique par altération testiculaire primaire. Au plan clinique, différentes procédures de recueil des spermatozoïdes testiculaires sont réalisées (TESE conventionnelle, micro-TESE, FNA/TESA, MESA, PESA) dont le choix dépend principalement de la cause de l’azoospermie (obstructive versus non obstructive) et des compétences du chirurgien. Au plan du laboratoire de fécondation in vitro, des procédures mécaniques d’extraction des spermatozoïdes du tissu peuvent être combinées avec un traitement enzymatique dans l’objectif d’accroitre le taux de récupération de spermatozoïdes. Plusieurs techniques ont été développées pour sélectionner des spermatozoïdes vivants chez les hommes n’ayant que des spermatozoïdes testiculaires immobiles. Toutefois, il manque des études bien construites et à effectifs consistants portant sur le bénéfice et l’innocuité d’une technique par rapport aux autres. Malgré toutes les méthodes et combinaisons de procédures de laboratoire disponibles qui ont comme objectif commun d’accroitre au maximum la récupération de spermatozoïdes dans les échantillons testiculaires, un grand nombre de patients avec NOA échouent à obtenir un enfant qui soit génétiquement leur. L’utilisation d’une technologie de pointe devrait améliorer les taux de récupération par la détection de foyers testiculaires ayant une spermatogenèse active et/ou l’identification de rare spermatozoïde isolé dans les suspensions testiculaires. D’autre part, la spermatogenèse in vitro ou la production de spermatozoïdes à partir de cellules souches embryonnaires ou de cellules souches pluripotentes induites pourraient constituer de futures options. Le présent article de revue résume les stratégies disponibles qui visent à maximiser la récupération de spermatozoïdes dans des échantillons extraits chirurgicalement.Bien que la technique d’injection intra cytoplasmique d’un spermatozoïde (ICSI) ait constitué une révolution dans le soulagement de l’infertilité masculine, l’utilisation de spermatozoïdes testiculaires lors de l’ICSI fut une découverte capitale auparavant inaperçue du traitement de l’homme azoospermique par altération testiculaire primaire. Au plan clinique, différentes procédures de recueil des spermatozoïdes testiculaires sont réalisées (TESE conventionnelle, micro-TESE, FNA/TESA, MESA, PESA) dont le choix dépend principalement de la cause de l’azoospermie (obstructive versus non obstructive) et des compétences du chirurgien. Au plan du laboratoire de fécondation in vitro, des procédures mécaniques d’extraction des spermatozoïdes du tissu peuvent être combinées avec un traitement enzymatique dans l’objectif d’accroitre le taux de récupération de spermatozoïdes. Plusieurs techniques ont été développées pour sélectionner des spermatozoïdes vivants chez les hommes n’ayant que des spermatozoïdes testiculaires immobiles. Toutefois, il manque des études bien construites et à effectifs consistants portant sur le bénéfice et l’innocuité d’une technique par rapport aux autres. Malgré toutes les méthodes et combinaisons de procédures de laboratoire disponibles qui ont comme objectif commun d’accroitre au maximum la récupération de spermatozoïdes dans les échantillons testiculaires, un grand nombre de patients avec NOA échouent à obtenir un enfant qui soit génétiquement leur. L’utilisation d’une technologie de pointe devrait améliorer les taux de récupération par la détection de foyers testiculaires ayant une spermatogenèse active et/ou l’identification de rare spermatozoïde isolé dans les suspensions testiculaires. D’autre part, la spermatogenèse in vitro ou la production de spermatozoïdes à partir de cellules souches embryonnaires ou de cellules souches pluripotentes induites pourraient constituer de futures options. Le présent article de revue résume les stratégies disponibles qui visent à maximiser la récupération de spermatozoïdes dans des échantillons extraits chirurgicalement.

Little is known about the manner in which motor behavior of the gross motor movements develops in early fetal period. Therefore, the goal of this study was to identify and classify the fetal distinct behavior patterns of the gross motor movements qualitatively in gestational weeks 10 through 17 (N = 69 fetuses). Using our unique Systematic Observation and Analysis Procedure based on conventional 2D ultrasound, we were able to identify the distinct behavior patterns with respect to the fetus' orientation (e.g., postural position and additional support by uterine wall) in real time and therefore distinguish 12 categories of behavioral patterns. The kappa coefficient for this procedure was 0.82, indicating high interobserver reliability. Interestingly, six of these 12 categories were not observed in gestational week 10–11, whereas all 12 movement categories were present in gestational week 16–17. Importantly, the occurrence of early development of gross motor control in utero emerges in the presence ofdynamic and interactive environmental factors, providing new insights into the fundamental aspects of developmental motor behavior in the growing infant. Highlights We developed a system for real-time monitoring of behavioral patterns of the gross motor movements with respect to the fetus' intrauterine orientation using a two-step, non-invasive observation protocol. Our monitoring system allowed us to detect twelve separate categories of distinct behavioral patterns of the gross motor movements in gestational week 10–17. Gross motor control develops in the early fetal period and is affected by the presence of dynamic and interactive environmental factors.

This retrospective cohort study followed a total of 364 women from their first fresh, donor intracytoplasmic sperm injection (ICSI) cycle through to up to six ICSI cycles. All patients started their treatment between January 2003 and December 2007. Live delivery after 25 weeks of gestation was the main outcome measure. The overall crude cumulative delivery rate (CDR) after six cycles was 66% while the overall expected CDR was 90%. In women aged 38-39 years, the crude and expected CDR after six cycles were 54% and 82%, respectively. In women aged 30-37 years, the crude and expected CDR after six cycles were 66% and 91%, respectively. In women aged 20-29 years the crude and expected CDR after six cycles were 81% and 93%, respectively. No significant difference was found between the CDR of patients who had a primary ICSI treatment (no previous intrauterine insemination) and patients who had previous intrauterine insemination. This study corroborates the impact of age on ICSI with donor spermatozoa.

Intracytoplasmic injection with testicular spermatozoa has become a routine treatment in fertility clinics. Spermatozoa can be recovered in half of patients with nonobstructive azoospermia. The use of immature germ cells for intracytoplasmic injection has been proposed for cases in which no spermatozoa can be retrieved. However, there are low pregnancy rates following intracytoplasmic injection using round spermatids from men with no elongated spermatids or spermatozoa in their testes. The in vitro culture of immature germ cells to more mature stages has been proposed as a means to improve this poor outcome. Several years after the introduction of intracytoplasmic injection with elongating and round spermatids, uncertainty remains as to whether this approach can be considered a safe treatment option. This review outlines the clinical and scientific data regarding intracytoplasmic injection using immature germ cells and in vitro matured germ cells.

STUDY QUESTION: Do cumulative live birth rates differ between single cleavage-stage Day 3 transfer and single blastocyst-stage Day 5 transfer? SUMMARY ANSWER: Cumulative live birth rates after Day 3 and 5 transfers were similar in young patients when the vitrified embryo transfers were also taken into account. WHAT IS KNOWN ALREADY: Previous evidence has shown that the probability of live birth following IVF with a fresh embryo transfer is significantly higher after blastocyst-stage Day 5 transfer. However, because the introduction of vitrification has enhanced the survival of cryopreserved embryos and improved pregnancy rates, the optimal outcome measure for this comparison should now be cumulative live birth rates, as these include the eventual contribution of vitrified-warmed embryos. STUDY DESIGN, SIZE, DURATION: Our retrospective study included first IVF/ICSI cycles performed between January 2010 and December 2013 at a tertiary care centre. PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients were scheduled for fresh single embryo transfer, either on Day 3 (n = 377) or on Day 5 (n = 623). Both IVF and ICSI cycles were included and the sperm used were either fresh or frozen partner ejaculates, or frozen donor ejaculates. The primary outcome was cumulative live birth (after 24 weeks) rate per started cycle, including the eventual contribution of vitrification until the birth of a first child. MAIN RESULTS AND THE ROLE OF CHANCE: Live birth rates per started cycle were significantly lower after transferring the fresh single cleavage-stage embryo, compared to a blastocyst (31.3% and 37.8%, respectively, P = 0.041). Furthermore, the number of embryo transfers necessary until the first live birth was significantly lower for blastocyst-stage embryos (P < 0.001). However, the cumulative live birth rates were 52.6% for cleavage-stage and 52.5% for blastocyst-stage transfers (P = 0.989). LIMITATIONS, REASONS FOR CAUTION: The extrapolation of the results is limited by the retrospective nature of the study. Furthermore, the analysis was restricted to patients under 36 years of age undergoing their first treatment cycle. WIDER IMPLICATIONS OF THE FINDINGS: These results deserve further clinical consideration in terms of time and cost efficiency. A subsequent analysis of the neonatal outcomes is necessary to confirm the safety of treatment cycles using extended culture. STUDY FUNDING/COMPETING INTERESTS: No external funding was received and there are no conflicts of interest to declare.

Menorrhagia is a common symptom in women at the end of their fertility lifespan, with leiomyomas being the most common cause. Although current treatment options for premenopausal menorrhagia consis...

STUDY QUESTION: Does vitrification of Day 3 and Day 5 embryos adversely affect birth outcomes of singletons and twins in comparison with peers born after fresh embryo transfer? SUMMARY ANSWER: Neonatal health parameters, including the prevalence of congenital malformations, in singletons and twins born after embryo vitrification are similar to or slightly better than after fresh embryo transfer. WHAT IS ALREADY KNOWN: Although vitrification, rather than slow-freezing, of embryos is routine practice nowadays, convincing evidence regarding the safety for the offspring is sparse. Literature data comprise results from mostly small-sized studies or studies including only Day 3 or only Day 5 vitrified embryo transfers. Overall, better or comparable perinatal outcomes, in terms of higher birthweight and lower risk for small-for-gestational age or for low birthweight, have been reported for singletons born after vitrified embryo transfer compared with fresh embryo transfer. According to the single available study with sufficient sample size, the congenital malformation rate was found to be comparable after vitrified and fresh embryo transfers. STUDY DESIGN, SIZE, DURATION: Data were collected from 960 cycles after transfer of embryos vitrified on Day 3 (n = 457) or Day 5 (n = 503) and from 1644 cycles after fresh embryo transfer on Day 3 (n = 853) or Day 5 (n = 791), performed between 2008 and 2013 at the Centre for Reproductive Medicine of the university hospital UZ Brussel. Outcome measures were neonatal health in terms of birthweight, small-for-gestational age, prematurity rate, perinatal death and major/minor/total malformation rate. PARTICIPANTS/MATERIALS, SETTING, METHODS: Perinatal health parameters of 11 stillborns and 1061 live borns (827 singletons and 234 twins) in the vitrified group and of 28 stillborns and 1838 live borns (1374 singletons and 464 twins) in the fresh embryo group are reported. Within 3 months after birth, children in the two study groups were assessed clinically with special attention tocongenital malformations by a paediatrician blinded to the type of embryo transfer. Data were analysed by multiple linear and logistic regression, adjusted for treatment variables and maternal characteristics. MAIN RESULTS AND THE ROLE OF CHANCE: Mothers to infants in the vitrified group were on average slightly older and more often suffering from pregnancy-related hypertensive disorders than mothers to infants in the fresh transfer group. Singletons born after vitrification showed a higher birthweight standard deviation score (SDS) (-0.4 versus -0.7; 95% confidence interval (CI): 0.0-0.3, P = 0.001) and a lower small-for-gestational age rate (AOR: 0.55; 95% CI: 0.34-0.90) in comparison with peers born after fresh embryo transfer. Preterm birth rate and perinatal death rate were comparable between the two groups (AOR: 0.91; 95% CI: 0.57-1.43 and AOR: 0.97; 95% CI: 0.40-2.36). In twins, neonatal outcomes including birthweight SDS, small-for-gestational age and prematurity rates were comparable in the vitrified and the fresh groups, when adjusted for confounders. Furthermore, the rate of major congenital malformations in live borns was comparable between the vitrified group and the fresh group, both in singletons (2.6 versus 2.8%; AOR: 0.91; 95% CI: 0.47-1.78) and in twins (2.4 versus 2.7%; AOR: 0.51; 95% CI: 0.05-5.72). Also, the total malformation rate in the vitrified group (3.4%; 95% CI: 2.4-4.8) did not differ from the rate in the fresh embryo group (3.9%; 95% CI: 3.1-5.0). The embryonic stage at vitrification or fresh transfer (cleavage-stage embryo or blastocyst) did not influence the birth characteristics or malformation rate. LIMITATIONS, REASONS FOR CAUTION: The main limitation of this study is the rather small twin group. Therefore, the outcome results for twins should be interpreted cautiously. WIDER IMPLICATIONS OF THE FINDINGS: This study provides evidence that transfer of vitrified Day 3 and Day 5 embryos does not adversely affect the neonatal health of the offspring in comparison with transfer of fresh embryos. Furthermore, neonatal outcomes were not different after transfer of vitrified blastocysts compared with transfer of vitrified cleavage-stage embryos. STUDY FUNDING/COMPETING INTERESTS: Educational grants for establishing and organizing the data collection have come from IBSA, Ferring, Organon, Shering-Plough and Merck. Merck Belgium funded the data collection for outcomes after vitrification between 2012 and 2015. All co-authors, except M.B., declared no conflict of interest. M.B. has received consultancy fees from Organon, Serono Symposia and Merck.

STUDY QUESTION: Is natural cycle frozen-thawed embryo transfer (NC-FET) associated with better clinical pregnancy rates (CPR) when compared to modified natural cycle frozen-thawed embryo transfer (mNC-FET)? SUMMARY ANSWER: NC-FET is associated with a higher CPR compared to mNC-FET. WHAT IS KNOWN ALREADY: There is conflicting evidence regarding the impact of hCG triggering on clinical outcomes after frozen-thawed embryo transfer (FET), and information on the effect of luteal phase support (LPS) is lacking. STUDY DESIGN, SIZE, DURATION: This retrospective study included all (n = 2353) consecutive cycles with FET of vitrified cleavage and blastocyst stage embryos warmed between January 2010 and April 2015 in a tertiary centre. The FET cycles were grouped by type as follows: NC (n = 501), NC + LPS (n = 828) or mNC + LPS (n = 1024). Artificial cycles were excluded from the analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: We performed mixed-effect multilevel multivariable regression analysis to account for the clustering of FETs using embryos derived from the same patient and/or ovarian stimulation cycle. Adjustment for the following potential confounders was also performed: female age at oocyte retrieval, number of oocytes retrieved, fresh cycle pregnancy outcome, embryo transfer rank, number of embryos transferred, embryo stage and grade and endometrial thickness. Bonferroni adjustment for multiple comparisons was performed whenever indicated. MAIN RESULTS AND THE ROLE OF CHANCE: The unadjusted CPR per cycle was significantly higher in the NC-FET group (46.9%) when compared with the mNC-FET + LPS groups (29.7%, P < 0.001) but not the NC-FET + LPS group (39.9%, P = 0.069). The lower clinical performance of mNC-FET + LPS remained significant even after adjusting for potential confounders [adjusted odds ratio (95% CI) compared to the NC-FET groups: 2.18 (1.64-2.90) and 1.67 (1.31-2.12) for the NC-FET and NC-FET + LPS groups, respectively]. A sensitivity analysis restricting the sample only to the first FET performed by the couple in our centre was also performed. The predicted CPR in this multivariable logistic regression model remained significantly higher in the NC-FET (53.9%) and NC-FET + LPS (44.9%) groups when compared to mNC-FET + LPS (34.2%, all Bonferroni-adjusted pairwise comparisons with P ≤ 0.01). LIMITATIONS, REASONS FOR CAUTION: The interpretation of the findings of this study is limited by the retrospective nature of the analysis and the potential for unmeasured confounding. WIDER IMPLICATIONS OF THE FINDINGS: The use of mNC-FET, using hCG triggering or progesterone supplementation, should be reconsidered in light of the potential negative effect on pregnancy outcome. STUDY FUNDING/COMPETING INTERESTS: None. TRIAL REGISTRATION NUMBER: N/A.

Study question Does the manipulation of gametes or embryos during ARTs increase the risk for monozygotic twinning (MZT)? Summary answer Frozen embryo transfer (ET) is associated with a lower MZT rate, while blastocyst culture is associated with an increased risk of monozygotic pregnancy. What is known already Monozygotic twins have a higher risk for perinatal complications. Although an increased incidence of monozygotic pregnancies after ART has been previously reported, data regarding the possible impact of different laboratory procedures are conflicting. Study design, size, duration All clinical pregnancies after single ET carried out in our centre between 2004 and 2013 (n = 6096) were retrospectively analysed for the incidence of MZT. The effect of different laboratory procedures on the incidence of MZT was evaluated. Participants/materials, setting, methods The following ART risk factors were assessed: maternal age, type of ET (fresh versus frozen), zona pellucida (ZP) manipulation (specifically, ICSI, embryo biopsy and assisted hatching), use of donor oocytes, embryo stage at time of ET (cleavage, compaction, early or advanced blastocyst) and culture media. Main results and the role of chance The overall MZT rate was 2.2% (136/6096). Frozen ET was associated with a significant reduction in MZT incidence (adjusted odds ratio (aOR) 0.48, 95% CI 0.29-0.80), while blastocyst transfer (early or advanced blastocyst) was associated with a significant increase in MZT risk (aOR 2.70, 95% CI 1.36-5.34; aOR 2.05, 95% CI 1.29-3.26, respectively). No significant differences were found between the MZT and singleton (non-MZT) groups regarding maternal age, the use of different ZP manipulation techniques, not type of culture media used. Limitation, reasons for caution This study is limited by its retrospective nature and the fact that monozygosity was not confirmed by genetic testing. Furthermore, since monozygotic pregnancy is a rare event, other ART parameters that may influence its incidence could not be assessed during our analysis. Wider implication of the findings Our findings warrant future studies designed to investigate the association between specific ART procedures and MZT, namely the potential risk of blastocyst transfer to increase MZT. Study funding/competing interests No external funding was used for this study. There are no conflicts of interest.

UNLABELLED: Guidelines in surgical treatment of mucinous ovarian neoplasms recommend the use of appendectomy as a measure to rule out a primary appendiceal origin of the ovarian tumor and proper staging. In extension this guideline is also applied for mucinous borderline ovarian tumors (mBOTs). As borderline ovarian tumors (BOTs) are often diagnosed postoperatively, most patients must undergo a second surgery to add appendectomy and staging to their surgical treatment. OBJECTIVE: To assess the role of appendectomy as part of the surgical treatment of mucinous BOTs. MATERIALS AND METHODS: A retrospective single institute based study was carried out. The authors evaluated the clinical charts of patients undergoing surgical treatment by a gynecologic oncologist in their institution for a mucinous BOT between January 1990 and January 2014. RESULTS: Twenty-seven patients were included. Appendectomy was performed in 30% of patients during primary or secondary surgical treatment. No appendiceal carcinoma was identified in any of the cases. Five patients already had a previous appendectomy. In eight patients the appendix was described as normal during surgery and left in place. For six patients the authors did not retrieve any information on previous appendectomy neither on the intraoperative state of the appendix. In the present overall study population, 78% showed no appendiceal involvement. For the remaining patients this information was missing. CONCLUSIONS: Secondary appendectomy to rule out a primary appendiceal origin of the mucinous BOT should not be performed when the appendix is described as grossly normal during primary laparoscopic surgery.

The present retrospective cohort study was conducted to investigate whether serum anti-Mullerian hormone (AMH) levels, determined by either the Immunotech (IOT) or the second generation (Gen II) assay, can predict follicular recruitment in women with polycystic ovary syndrome (PCOS) undergoing ovulation induction with clomiphene citrate (CC). Patients received 50 mg CC daily for ovulation induction followed by natural intercourse or intrauterine insemination. Overall, 84 women had their serum AMH levels tested before treatment [42 patients with Immunotech (IOT), and 42 patients with the Gen II assay]. The primary outcome was to determine dominant follicle (>10 mm) recruitment in relation to AMH levels. Thirty-three (79%) patients in the IOT and 34 (81%) patients in the Gen II assay group developed a dominant follicle within 15 days after initiation of CC. Circulating AMH levels did not differ between women with or without dominant follicular recruitment in the both groups. By using either the AMH IOT or the Gen II assay, serum AMH levels were not predictive of the development of a dominant follicle. In conclusion, serum AMH levels measured by IOT or Gen II assay, has limited value to predict PCOS patients who will develop a dominant follicle following ovulation induction with CC.

STUDY QUESTION: What is the effect of vitamin D deficiency on the pregnancy rates following frozen embryo transfer (FET)?. SUMMARY ANSWER: Vitamin D deficiency does not affect pregnancy rates in FET cycles. WHAT IS KNOWN ALREADY: Although there is evidence that the potential impact of vitamin D deficiency on reproductive outcome may be mediated through a detrimental effect on oocyte or embryo quality, the rationale of our design was based on evidence derived from basic science, suggesting that vitamin D may have a key role in endometrial receptivity and implantation. Only few retrospective clinical studies have been published to date with conflicting results. STUDY DESIGN, SIZE, DURATION: This study is the first prospective observational cohort study from the Centre for Reproductive Medicine at the University Hospital of Brussels. The duration of the study was 1 year. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 280 consecutive patients, who had at least one blastocyst frozen and were planned for a FET, were enrolled in the study following detailed information and signing of a written informed consent. Serum analysis of 25-OH vitamin D was measured on the day of embryo transfer, and the impact of vitamin deficiency was investigated on reproductive outcomes. MAIN RESULTS AND THE ROLE OF CHANCE: Among all patients, 45.3% (n = 127) had vitamin D deficiency (

Carriers of reciprocal translocations (rcp) are known to be at risk for reproductive difficulties. Preimplantation genetic diagnosis (PGD) is one of the options these carriers have to try in order to fulfil their desire to have a child. In the present study, we retrospectively looked at the results of 11 years (1997-2007) of PGD for rcp in our center to improve the reproductive counseling of these carriers. During this period 312 cycles were performed for 69 male and 73 female carriers. The mean female age was 32.8 years, the mean male age 35.8 years. Most carriers were diagnosed with a translocation because of fertility problems or recurrent miscarriages, and most of them opted for PGD to avoid these problems. In 150 of the 312 cycles, embryo transfer (ET) was feasible and 40 women had a successful singleton or twin pregnancy. This gives a live birth delivery rate of 12.8% per started cycle and of 26.7% per cycle with ET. Owing to the large number of abnormal embryos, PGD cycles for rcp often lead to cancellation of ET, explaining the low success rate when expressed per cycle with oocyte pick-up. Once ET was feasible, the live birth delivery rate was similar to that of PGD in general at our center. PGD is therefore an established option for specific reciprocal translocation carriers.

background: Complete asthenozoospermia, i.e. 100% immotile spermatozoa in the ejaculate, is reported at a frequency of 1 of 5000 men. Its diagnosis implies a poor fertility prognosis even with ICSI. It is extremely important to distinguish between two different groups of patients with complete asthenozoospermia, i.e. virtual or absolute asthenozoospermia. With the former group having some motile sperma- tozoa after extensive processing of the semen, absolute asthenozoospermia can be associated with metabolic deficiencies, ultrastructural abnormalities of the sperm flagellum, necrozoospermia otherwise it can be idiopathic. In the management of persistent absolute astheno- zoospermia, it is very important to elucidate its nature and whenever possible to correct the potential causes. methods: We reported data published in the literature on the aetiology of absolute asthenozoospermia and the different techniques to improve ICSI outcome. We propose an algorithm for diagnosis and treatment of this condition. results: Different results regarding fertilization, cleavage and pregnancy rate have been published in patients with absolute asthenozoos- permia undergoing ICSI. However, the results vary widely depending on the sperm origin and the technique applied for immotile sperm selection. The percentage of viable spermatozoa varies between 0 and 100%. conclusions: Absolute immotile spermatozoa is one of the most important causes of reduced fertilization and pregnancy rates after ICSI and different techniques are used to improve ICSI outcomes. However, it still remains unclear which is the best technique to improve the pregnancy outcomes in these couples.

Pseudomyxoma peritonei is only rarely seen in conjunction with primary ovarian tumors. It has been suggested that only ruptured mucinous tumors arising in ovarian mature cystic teratomas can result in this clinical picture. We describe a case of a late invasive recurrence of a mucinous intestinal-type borderline ovarian tumor arising from a mature teratoma after complete surgical debulking. Borderline ovarian tumors behave indolently in the overwhelming majority of cases, and the prognosis is therefore usually outstanding.

Our objective was to determine the perinatal outcome of first- and second-born twins compared to singletons, born at the same gestational age. To that end we conducted a case-control study in Flanders (Northern Belgium). During a 10-year period (01.01.1999–31.12.2008), the entire twin population — 11,154 first- and 11,118 second-born twins (cases) — was compared to 22,228 singletons (controls) with respect to fetal and neonatal (0–27 days) mortality. Only case and control infants of ≥ 500 grams were included, which explained the unequal number of first- and second-born twins. Mothers and their infants of cases and of controls were derived from the Flemish perinatal database and were matched for maternal age and parity, gestational age and gender of the offspring. The main outcome measures were fetal and neonatal mortality according to gestational age. The frequency of fetal death was statistically significantly less frequent in preterm born twins than in singletons, except at term where the reverse was seen in second-born twins compared to controls. After adjustment for congenital malformations, the results stayed unchanged. Below 28 weeks gestation, singletons had a significantly lower neonatal mortality rate than twins that persisted after adjustment for congenital malformations: the first-born twin versus singleton OR 1.71 (1.17–2.51) and second-born versus singleton OR 2.09 (1.43–3.05). Between 28 and 32 weeks, the second-born twin showed a survival advantage over the control singleton. Between 32 and 36 6/7 weeks both twins had a significantly higher survival rate than the corresponding singleton controls. However, after adjustment for congenital malformations, the aforementioned differences between 28 and 36 6/7 weeks disappeared. When at term, twins and singletons had a comparable, though very low, neonatal death rate. These results confirm previous published data. In conclusion, we demonstrated that the neonatal death rate was lower for twins between 32 and 36 weeks (from 28 weeks for the second born twin) when compared to a singleton of the same gestational age. After adjusting for congenital malformations, there was no statistical significant difference.

BACKGROUND: Only 13 cases of pyomyoma related to pregnancy have been described since 1945. Treatment consists of hysterectomy, which exposes critically ill patients to operative risks and induces infertility. CASES: Three cases of pyomyoma in the postpartum period are described. Treatment using computed tomography-guided drainage was realized successfully in two cases. CONCLUSION: Therapy via drainage and lavage of pyomyoma is a viable option to preserve patient fertility. In the absence of a proper response to this treatment, total abdominal hysterectomy is the treatment of choice. PMID

background: Although cryopreservation of semen is a routine procedure for preserving male gametes, an efficient method of preserving fertility through oocyte freezing has only recently become available for women. In view of the limited female reproductive lifespan, oocyte freezing can now offer women some protection against the decline in fertility with aging. methods: A survey was performed in Belgium among 1914 women of reproductive age (21 –40 years) to assess public attitudes towards the phenomenon called ‘social oocyte freezing’. Women were questioned on their awareness of the age-related fertility decline and their views and intentions towards considering undergoing oocyte cryopreservation. results: The electronic questionnaire was completed by 1049 women, giving a response rate of 55%, and 25 were excluded as they were incomplete/inconsistent. Our results demonstrate that 31.5% of respondents consider themselves as potential social oocyte freezers, of which 3.1% would definitely consider the procedure. Just over half of the women (51.8%) would not consider the procedure while 16.7% indicated they had no opinion. Potential oocyte freezers are characterized by a higher number of desired children and more openness to oocyte donation. The decision to actually embark on such treatment would primarily depend on conditions, such as the procedure not affecting their natural fertility and the health of future children. conclusions: We conclude that a significant proportion of young women would consider safeguarding their reproductive potential or are at least open to the idea of social oocyte freezing.

background: In order to optimize blastocyst cryopreservation, vitrification was introduced as the routine procedure instead of slow freezing. The outcome of a closed blastocyst vitrification system was evaluated in relation to the blastocyst score before cryopreservation in single embryo transfers (SETs). methods: Supernumerary blastocysts of IVF/ICSI patients with a fresh Day 5 transfer were vitrified using CBS-VIT High Security (HS) straws. In 759 warming cycles, morphological survival and transfer rates were assessed in relation to the blastocyst score and the day of vitrification. Pregnancy rates were assessed in 530 SET and 156 double embryo transfer (DET) cycles. Implantation rates per embryo transferred in SET cycles were analysed according to blastocyst quality and day of cryopreservation. results: Immediate morphological survival was 77.8% (921/1185) and the transfer rate per warmed blastocyst was 70.7% (838/1185). Survival rates were higher for Day 5 early blastocysts (86.7%) compared with full (78.7%) or expanded blastocysts (72.7%). A reduced survival rate of 70.1% was found for Day 6 blastocysts compared with Day 5 blastocysts (80.6%, P , 0.001). The overall clinical/ongoing pregnancy rate after SET was 16.4/14.2% and 24.4/20.5% after DET with an ongoing multiple pregnancy rate of 21.8% (7/32) after DET. Significantly lower implantation rates were found for Day 5 early blastocysts (10.6%) compared with advanced blastocysts (17.5%, P , 0.05). Similar implantation potentials for Day 5 and 6 blastocysts (14.3 versus 13.7%) were found. conclusions: Successful cryopreservation of blastocysts from the early cavitating up to expanded blastocyst stages is possible using a closed HS device. The choice between single or double frozen blastocyst transfer should depend on blastocyst expansion after vitrification.

INTRODUCTION: The aim was to evaluate the postoperative morbidity and outcome of palliative endoscopic resections for relief of infravesical obstruction in prostate cancer patients with hormone deprivation therapy, and to investigate the added value of bipolar technology over conventional monopolar resections. MATERIAL AND METHODS: A retrospective study was performed on 70 patients with prostate cancer under hormone deprivation therapy undergoing 75 endoscopic procedures, by either monopolar or bipolar technology, between August 2005 and March 2009 at a single institution. The analysis used outpatient, inpatient, and operative records, and observations of electrolyte changes in the serum, postoperative morbidity, and the overall results of palliative endoscopic resections. Preoperative cancer stages and grades were compared with the pathological findings after surgery. Postoperative outcome and complications of conventional monopolar and bipolar technology were compared. RESULTS: Over a period of 44months, 34 conventional monopolar resections were performed in 32 patients and 41 bipolar resections in 38 patients. Patients' profiles regarding age, initial cancer stage and grade, resection weight, resection speed, catheterization time, and hospital stay were similar in both groups. No statistically significant difference was observed in sodium drop (p = 0.802), clot retention (p = 0.565), or urinary retention (p = 0.292). The overall success rate in relieving obstruction leading to spontaneous voiding was 77%. While 38% of the patients had a high grade tumour at diagnosis, 79% were found to be high grade after the endoscopic resection (p

BACKGROUND: Currently, no published data exist about the gonadal function of children born after ICSI. To evaluate potential risk of testicular seminal dysfunction in boys born to fathers with compromised spermatogenesis, serum inhibin B (as a marker for spermatogenesis) was assessed. METHODS: We recruited 50 pubertal adolescents from the oldest cohort of infants born following ICSI. Cross-sectional serum inhibin B levels of all 50 ICSI adolescents, and longitudinal serum inhibin B (assessed at 8 and 14 years) in 25 boys, are reported. RESULTS: A statistically significant increase in inhibin B levels was observed between 8 (mean 69 ng/l, SD ± 35) and 14 years (mean 145 ng/l, SD ± 41; P < 0.001). In three quarters of the ICSI boys an increase in serum inhibin B levels of at least 30% between 8 and 14 years was observed. In all but 4 of the 14-year-old ICSI boys serum inhibin B was normal. Serum inhibin B levels in boys from fathers with severe oligozoospermia did not differ from concentrations in boys from fathers without severe oligozoospermia (154 ± 51 and 142 ± 47 ng/l, respectively; P = 0.4). CONCLUSIONS: The majority of ICSI boys have a significant increase in serum inhibin B, attaining normal values for pubertal status at the age of 14 years. ICSI adolescents from fathers with severely compromised spermatogenesis do not have lower inhibin B levels than those with fathers with normal spermatograms. Further follow-up of the spermatogenic potential of ICSI teenagers up to young adulthood is mandatory to confirm a normal reproductive capacity.

INTRODUCTION: the purpose of this retrospective analysis is to compare the efficiency of hCG-induced natural and Clomiphene citrate (CC) cycles in normovulatory patients undergoing frozen embryo transfer (FET). MATERIALS AND METHODS: it was retrospectively conducted in the Dutchspeaking Free University of Brussels and covered the period from April 2003 to August 2006. In particular, 428 day-three FET cycles belonging to the two comparative groups were recruited. Of these FET cycles, 261 were hCG-induced natural and 167 clomiphene citrate-induced cycles. RESULTS: no statistically significant difference was observed in live birth rate between CC and natural group (22.2% versus 22.6%), respectively (P = 0.708). Except for the number of embryos transferred (1.72 ± 0.46 for cc group versus 1.63 ± 0.48 for natural group, p = 0.045), no other parameters seem to influence the outcome. discussion: To our knowledge, this is the first attempt to investigate which of the above mentioned regimens is optimal for normo-ovulatory women in FET cycles. A similar delivery outcome was observed for hCG-induced natural and CC-induced cycles used for endometrial preparation in FET.

BACKGROUND A concern for new compounds in fertility treatment is the possible risk of perinatal complications or birth defects. To demonstrate long-term safety of ganirelix (GnRH antagonist) treatment in controlled ovarian stimulation (COS), follow-up data on pregnancy and neonatal outcome were analysed for 1000 fetuses (>/=16 gestational weeks). METHODS Obstetrical and neonatal data on 839 pregnancies, resulting in 969 live born infants after ganirelix treatment were compared with a historical cohort of 753 pregnancies after long GnRH agonist (buserelin) treatment, resulting in 963 live born infants. All treatment cycles were performed in a single fertility centre. The infants were examined at the Universitair Ziekenhuis Brussel using an identical follow-up protocol. Incidence of major malformations (i.e. causing functional impairment or requiring surgical correction) was the primary end-point and was analysed by logistic regression including treatment, age of mother, IVF method and pregnancy type (singleton/multiple) as independent variables. RESULTS There were no relevant differences in maternal characteristics, fertilization method and pregnancy and delivery complications between the ganirelix and historical GnRH agonist groups. There were relatively more multiple pregnancies in the historical GnRH agonist group (31.9%) than the ganirelix group (18.7%; P /=26 weeks was 5.0% in the ganirelix cohort versus 5.4% in the historical GnRH agonist group (odds ratio 0.94, 95% confidence interval, 0.62-1.42). CONCLUSION In terms of neonatal outcome and risk of major malformations, treatment with the GnRH antagonist ganirelix during COS is as safe as traditional GnRH agonists. ClinicalTrials.gov identifier NCT00724789.

About 30% of monochorionic twin pregnancies are complicated by twin-to-twin transfusion syndrome (TTTS), isolated discordant growth, twin anemia-polycythemia sequence, congenital defects or intrauterine demise. About 15% will be eligible for invasive fetal therapy, either fetoscopic laser treatment for TTTS or fetoscopic or ultrasound-guided umbilical cord coagulation for a severe congenital defect in one twin or severe discordant growth with imminent demise of the growth-restricted twin. Ultrasound examination in the first and early second trimester can differentiate the monochorionic twins at high risk for adverse outcome from those likely to be uneventful, which may be useful for patient counselling and planning of care.

Objectives To test the validity of the myocardial performance index (MPI) and its components against the more conventional methods of fetal cardiac function assessment: the ejection fraction (EF) for systolic function and the E/A index (ratio of transmitral flow during early (E) ventricular filling to flow during atrial (A) contraction) for diastolic function, both in a normal population and in a population at risk for cardiac failure because of volume overload (recipient fetuses in cases of twin–twin transfusion syndrome (TTTS)). Methods The MPI was measured prospectively in addition to more commonly used indices of systolic (EF) and diastolic (E/A index) cardiac function in 117 healthy fetuses (gestational age range, 20–36 weeks) and in 14 fetuses suspected of cardiac failure because of the presence of TTTS. Nomograms were constructed for all variables, and correlations between the MPI, EF and E/A index were assessed. The time taken to obtain the measurements as well as the interobserver and intraobserver variability were determined for the MPI and EF. Results In healthy fetuses, the MPI and EF were independent of gestational age, whereas the E/A index and isovolumetric relaxation time (IRT) increased with gestational age. The MPI correlated inversely with the EF (P < 0.001). The IRT showed a trend towards an inverse correlation with the E/A index (P = 0.10). The mean ± SD time needed to measure the MPI and EF was 140 ± 65 s and 185 ± 187 s, respectively (P = 0.43). Interobserver and intraobserver intraclass correlation coefficients for the MPI were 0.98 (95% CI, 0.85–0.99) and 0.82 (95% CI, 0.14–0.95), respectively; those for the EF were 0.58 (95% CI, − 0.16 to 0.85) and 0.51 (95% CI, − 0.46 to 0.83), respectively; and those for the E/A index were 0.97 (95% CI, 0.88–0.99) and 0.91 (95% CI, 0.66–0.98), respectively. All variables, except ejection time, were significantly different between normal fetuses and those with TTTS. Conclusions The MPI is an indicator of the systolic component of fetal left ventricular function that can be easily acquired and reproduced. The MPI is strongly correlated with the EF but shows less interobserver and intraobserver variability. Copyright © 2008 ISUOG. Published by John Wiley & Sons, Ltd.

OBJECTIVE To determine the extent to which computer-aided ultrasonography of the prostate (HistoScanningTM, Advanced Medical Diagnostics, Waterloo, Belgium) can identify tumour foci that correspond to a volume of ≥0.50 mL. PATIENTS AND METHODS Between September 2004 and February 2006, 29 men were HistoScanned before scheduled radical prostatectomy. The three-dimensional raw (grey-scaled) data required for HistoScanning analysis were acquired by transrectal ultrasonography, and analysed using organ-specific tissue-characterization algorithms which form the core of the HistoScanning technology. The HistoScanning analysis results were compared with the histology of the whole-mounted prostate, step-sectioned sagittally at 5-mm intervals, and each slide analysed by 5 × 5 mm grid analysis. RESULTS Of 29 patients, 13 had histology unknown to those evaluating the HistoScanning data. With 0.50 mL as the lower threshold for delineating and visualizing cancer volume, HistoScanning correctly predicted the presence of all 12 lesions that were subsequently confirmed to occupy ≥0.50 mL. In addition three lesions were predicted as being present and of ≥0.50 mL. These three lesions were subsequently confirmed to be present but were ≤0.50 mL on histopathological review. Thus, using the clinically accepted volume threshold of 0.50 mL, the sensitivity, specificity, positive and negative predictive value of HistoScanning were 12/12, 13/16 (82%), 12/15 (80%) and 12/12, respectively, for the cancer foci analysed. CONCLUSIONS In this preliminary study, HistoScanning accurately detected cancer foci of ≥0.50 mL; these encouraging results will need to be verified in a larger group of patients.

Objective To determine the incidence, characteristics, and evolution of sensorineural hearing loss (SNHL) in infants with a congenital cytomegalovirus infection (cCMV). Study design In a prospective 10-year study, 14 021 unselected live-born infants were screened for cCMV by virus isolation in urine. Congenitally infected newborns were evaluated for SNHL during the first 5 years of life. Results A total of 74 of the 14 021 infants (0.53%) were congenitally infected; of these, 4 (5.4%) were symptomatic at birth. Hearing testing could be performed in 60 of the infants. SNHL was found in 21% of the asymptomatic and in 33% of symptomatic congenitally infected infants. Late-onset hearing loss was detected in 5%, progression in 11%, fluctuation in 16%, and improved hearing threshold in 18% of the infants with cCMV. SNHL was observed in 15% of infected infants born after a maternal primary infection, in 7% born after a maternal recurrent infection, and in 40% after a maternal infection of indeterminate timing. Conclusions In our study population, 0.53% of the infants had cCMV infection, 22% of whom developed SNHL. Long-term follow up and repeated audiologic testing is needed, because progression, fluctuation, improvement, and late-onset hearing loss are important features of cCMV infection. The search for a neonatal screening program to detect all cCMV is worthwhile.

Belfort et al. (Aug. 13 issue)1 report that fetal electrocardiographic (ECG) ST-segment analysis (STAN) combined with conventional intrapartum electronic fetal heart-rate monitoring did not improve perinatal outcomes or decrease operative-delivery rates, as compared with conventional monitoring. However, other randomized trials2,3 with adequate power have shown that strict use of the International Federation of Gynecology and Obstetrics classification for cardiotocography (FIGO-CTG) and STAN guidelines resulted in a relative decrease of 46% in the rate of operative vaginal deliveries (P

STUDY QUESTION: Does closed oocyte vitrification in an oocyte donation programme have an impact on obstetric and neonatal outcome? SUMMARY ANSWER: Obstetric and neonatal outcomes after closed system vitrification of donor oocytes appear to be reassuring. WHAT IS KNOWN ALREADY: The use of fresh oocytes has not been proved to be superior to the use of vitrified donor oocytes in terms of survival, embryo development and clinical pregnancies. Those studies used open devices to prove the non-superiority. Very limited information is available on the comparison of open and closed devices, and the results for survival, embryo development and pregnancy outcomes are conflicting. Data on obstetric and neonatal outcome from vitrified oocytes are scarce. Only one large report is available after the use of donor oocytes vitrified with an open device. STUDY DESIGN, SIZE, DURATION: Retrospective observational study performed at the Centre for Reproductive Medicine, UZ Brussel, Belgium. All 117 oocyte recipient cycles between March 2010 and August 2014 with the use of a closed vitrification device and leading to a pregnancy beyond 20 weeks were included in this study. PARTICIPANTS/MATERIALS, SETTING, METHODS: All recipient warming cycles with a pregnancy beyond 20 weeks from vitrified donor oocytes: results from the fresh embryo transfers. MAIN RESULTS AND THE ROLE OF CHANCE: For 117 recipient cycles, a total of 793 oocytes were warmed of which 657 (82.8%) survived and 499 (76.0%) were fertilized. Nineteen single and 98 double embryo transfers led to 95 singleton and 22 twin pregnancies. Hypertensive disorders, haemorrhages and gestational diabetes were reported in 22/112 (19.6%), 30/112 (26.8%) and 13/112 (11.6%) of the pregnancies, respectively. No major adverse neonatal outcomes were observed. Congenital malformations were observed in 11 out of 139 children; for one an elective termination was performed at 25 weeks. LIMITATIONS, REASONS FOR CAUTION: Since March 2010, almost all oocytes for donation are vitrified in our centre. Therefore, no recent data are available to control the outcomes of fresh oocyte donations. WIDER IMPLICATIONS OF THE FINDINGS: The reassuring results obtained in the current study show that closed system vitrification devices for donor oocytes may be used as an alternative to open devices which have been linked to possible cross-contamination issues. STUDY FUNDING/COMPETING INTERESTS: None. TRIAL REGISTRATION NUMBER: N/A.

In two prospective uncontrolled feasibility trials, we examined the effect of corifollitropin alfa (CFA) followed by highly purified human menopausal gonadotrophin (hpHMG) in a short flare-up gonadotropin-releasing hormone (GnRH) agonist and a long GnRH agonist protocol for women with poor ovarian response. Overall, 45 patients were treated with short flare-up and 47 patients with the long agonist protocol. All patients received a single dose of 150 μg CFA, followed by 300 IU hpHMG 7 days later, triggering with 10 000 IU hCG, CSI and day 3 embryo transfer. Ongoing pregnancy rates (OPRs) did not differ between the short 15.6% and the long 17% agonist protocol (p = 0.85). Among patients treated with the short flare-up protocol, OPRs were 20% for younger patients (